MiR‐17‐5p‐engineered sEVs Encapsulated in GelMA Hydrogel Facilitated Diabetic Wound Healing by Targeting PTEN and p21

Abstract Delayed wound healing is a major complication of diabetes, and is associated with impaired cellular functions. Current treatments are unsatisfactory. Based on the previous reports on microRNA expression in small extracellular vesicles (sEVs), miR‐17‐5p‐engineered sEVs (sEVs 17‐OE ) and encapsulated them in gelatin methacryloyl (GelMA) hydrogel for diabetic wounds treatment are fabricated. SEVs 17‐OE are successfully fabricated with a 16‐fold increase in miR‐17‐5p expression. SEVs 17‐OE inhibited senescence and promoted the proliferation, migration, and tube formation of high glucose‐induced human umbilical vein endothelial cells (HG‐HUVECs). Additionally, sEVs 17‐OE also performs a promotive effect on high glucose‐induced human dermal fibroblasts (HG‐HDFs). Mechanism analysis showed the expressions of p21 and phosphatase and tensin homolog (PTEN), as the target genes of miR‐17‐5p, are downregulated significantly by sEVs 17‐OE . Accordingly, the downstream genes and pathways of p21 and PTEN, are activated. Next, sEVs 17‐OE are loaded in GelMA hydrogel to fabricate a novel bioactive wound dressing and to evaluate their effects on diabetic wound healing. Gel‐sEVs 17‐OE effectively accelerated wound healing by promoting angiogenesis and collagen deposition. The cellular mechanism may be associated with local cell proliferation. Therefore, a novel bioactive wound dressing by loading sEVs 17‐OE in GelMA hydrogel, offering an option for chronic wound management is successfully fabricated.